KOGISO Tomomi    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Non peer reviewed
Title	A genome-wide association study identifying SVEP1 variant as a predictor of response to tolvaptan for cirrhotic ascites.
Journal	Formal name：Liver international Abbreviation：Liver Int ISSN code：14783231/14783223
Domestic / Foregin	Foregin
Volume, Issue, Page	41(12),pp.2944-2953
Author and coauthor	Kawaratani Hideto, Sawai Hiromi, Onishi Masaya, Kogiso Tomomi, Shimada Noritomo, Uojima Haruki, Nakajima Tomoaki, Matsumoto Naoki, Ikejima Kenichi, Ishikawa Toru, Terai Shuji, Motoyama Hiroyuki, Komori Atsumasa, Hirashima Noboru, Saito Satoru, Eguchi Yuichiro, Nojima Masanori, Kawai Yosuke, Tateyama Masakuni, Yoshiji Hitoshi, Tanaka Yasuhito
Publication date	2021/12
Summary	BACKGROUND & AIMS:Tolvaptan, vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan's efficacy for patients with hepatic ascites.METHODS:From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; >1.5 kg decrease of BW) were included in the GWAS and replication study.RESULTS:Genome-wide association study showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 × 10-8 ). Multivariate analyses showed that serum sodium (Na), blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 0.92, P = .003; OR = 1.02, P = .02 and OR = 3.98, P = .000008, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (=exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774.CONCLUSION:SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score (>38.6%) can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.
DOI	10.1111/liv.15022
PMID	34309184